Revised chronology of Neogene DSDP holes from the World Ocean

After nearly 30 years of growth in geochronologic knowledge, the originally published age models for many older deep sea marine sections have become badly outdated. In this report we present newly revised age models for Neogene sediments from 94 DSDP holes. Biostratigraphic data for planktonic foraminifers, calcareous nannofossils, diatoms and radiolarians, paleomagnetic and other stratigraphic data were compiled from the original Initial Reports volumes of DSDP. The Berggren et al. (1985 doi:10.1130/0016-7606(1985)96<1407:CG>2.0.CO;2) scale was used for the age of magnetic reversals, and a variety of recent papers were used to establish a standard modern set of calibrations for marine microfossil events to the magnetic reversal scale. New age vs depth plots were made for each hole, and for each a new line of correlation was created. All tabulated stratigraphic data, new age models, and age depth plots are given as appendices to the report.

Pacific Neogene carbonate accumulation rates

I have compiled CaCO3 mass accumulation rates (MARs) for the period 0-25 Ma for 144 Deep Sea Drilling Project and Ocean Drilling Program drill sites in the Pacific in order to investigate the history of CaCO3 burial in the world's largest ocean basin. This is the first synthesis of data since the beginning of the Ocean Drilling Program. Sedimentation rates, CaCO3 contents, and bulk density were estimated for 0.5 Myr time intervals from 0 to 14 Ma and for 1 Myr time intervals from 14 to 25 Ma using mostly data from Initial Reports volumes. There is surprisingly little coherence between CaCO3 MAR time series from different Pacific regions, although regional patterns exist. A transition from high to low CaCO3 MAR from 23-20 Ma is the only event common to the entire Pacific Ocean. This event is found worldwide. The most likely cause of lowered pelagic carbonate burial is a rising sea-level trend in the early Miocene. The central and eastern equatorial Pacific is the only region with adequate drill site coverage to study carbonate compensation depth (CCD) changes in detail for the entire Neogene. The latitude-dependent decrease in CaCO3 production away from the equator is an important defining factor of the regional CCD, which shallows away from the equatorial region. Examination of latitudinal transects across the equatorial region is a useful way to separate the effects of changes in carbonate production ('productivity') from changes in bottom water chemistry ('dissolution') upon carbonate burial.

Revised Cenozoic hiatus database

The differential effects of climate change, sea level, and water mass circulation on deposition/erosion of marine sediments can be constrained from the distribution of unconformities in the world's oceans. I identified temporal and depth patterns of hiatuses ("hiatus events") from a large and chronologically well constrained stratigraphic database of deep-sea sediments. The Paleogene is characterized by few, several million year long hiatuses. The most significant Cenozoic hiatus event spans most of the Paleocene. The Neogene is characterized by short, frequent hiatus events nearly synchronous in shallow and deep water sediments. Epoch boundaries are characterized by peaks in deep water hiatuses possibly caused by an increased circulation of corrosive bottom water and sediment dissolution. The Plio-Pleistocene is characterized by a gradual decrease in the frequency of hiatuses. Future studies will focus on the regional significance of the hiatus events and their possible causes.

Middle Miocene to Quaternary diatom biostratigraphy of DSDP Site 90-594

A diatom biostratigraphy is presented for middle Miocene through Quaternary sediments recovered from the Chatham Rise east of New Zealand's South Island. The upper 590 m of the 639.5-m composite-section Site 594 represents approximately 16 m.y. and is characterized by moderately to very poorly preserved diatoms of antarctic to temperate affinity. Pliocene through Quaternary assemblages are poorly preserved and dominated by antarctic-subantarctic species which provide detailed biostratigraphic control. Recognized are 11 of 14 zones of the middle upper Miocene to Quaternary Neogene Southern Ocean diatom zonation (NSD 7-NSD 20) of Ciesielski (1983; this chapter). Four Neogene Southern Ocean diatom zones (NSD 3-NSD 6) are recognized in the lower middle Miocene to middle upper Miocene of Site 594. Assemblages of this interval have a mixed high-latitude and temperate affinity; however, poor preservation limits correlation to high- and temperate-latitude zonal schemes. Neogene North Pacific diatom zones and subzones of NNPD 3 through NNPD 5 (Barron, in press, b) are correlated to Neogene Southern Ocean diatom zones NSD 3 through NSD 7: the upper portions of the Actinocyclus ingens Zone (NNPD 3) is correlative to the upper Nitzschia maleinterpretaria Zone (NSD 3); the Denticulopsis lauta Zone (NNPD 4) and Subzones a and b are correlative to the lower Coscinodiscus lewisianus Zone (NSD 4); and the D. hustedtü-D. lauta Zone (NNPD 5) and its Subzones a through d encompass the upper C. lewisianus Zone (NSD 4), N. grossepunctata Zone (NSD 5), N. denticuloides Zone (NSD 6), and the lower D. hustedtii-D. lauta Zone (NSD 7). A major disconformity spans the late Gilbert to early Gauss Chron (3.9-2.8 Ma). A second disconformity brackets the Miocene/Pliocene boundary; the section missing covers late Chron 5 and the early Gilbert chron (5.5-4.6 Ma). The remainder of the siliceous-fossil-bearing Miocene sediments at Site 594 appear to be correlative to lower paleomagnetic Chronozone 5 through upper Chronozone 16. Uppermost lower Miocene or lowermost middle Miocene sediments in the basal 50 m of Hole 594A are barren of diatoms.

Recruitment and training of board members for the 90's and beyond

An historical analysis of the management of the arts in Australia in the last fifty years demonstrates clearly the problems faced by arts organisations which have poorly selected and trained Boards of Directors. Traditionally Board members were selected because they represented the various facets and skills involved in business (marketing, law, accountancy, management, entrepreneurship) or they were arts practitioners or patrons, or they had some particular social standing. Arts organisations recruited Board members like a "mixed bag of lollies - one of these and one of those". No consideration was given to the vital qualities of enthusiasm, reliability, empathy, capacity for hard work, strong arts interest, effective communication skills and respect for organisational processes.

The heat shock protein 90 inhibitor, 17-allylamino-17- demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line

Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence and severity, few effective therapies exist. To address this, we examined whether the heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast cancer metastasis to bone. Utilizing the human breast cancer subline, MDA-MB-231SA, previously in vivo selected for its enhanced ability to generate osteolytic bone lesions, we determined that 17-AAG potently inhibited its in vitro proliferation and migration. Moreover, 17-AAG significantly reduced MDA-MB-231SA tumor growth in the mammary-fat pad of nude mice. Despite these findings, 17-AAG enhanced the incidence of bone metastasis and osteolytic lesions following intracardiac inoculation in the nude mouse. Consistent with these findings, 17-AAG enhanced osteoclast formation 2- to 4-fold in mouse bone marrow/osteoblast cocultures, receptor activator of nuclear factor κB ligand (BANKL)-stimulated bone marrow, and RAW264.7 cell models of in vitro osteoclastogenesis. Moreover, the drug enhanced osteoclastogenesis in human cord blood progenitor cells, demonstrating that its effects were not limited to mouse models. In addition to 17-AAG, other Hsp90 inhibitors, such as radicicol and herbimycin A, also enhanced osteoclastogenesis. A pro-osteolytic action of 17-AAG independent of tumor presence was also determined in vivo, in which 17-AAG-treated tumor-naive mice had reduced trabecular bone volume with an associated increase in osteoclast number. Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence causedby 17-AAG in vivo. These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial.

Comparison of fractional and geodesic anisotropy in diffusion tensor images of 90 monozygotic and dizygotic twins

We used diffusion tensor magnetic resonance imaging (DTI) to reveal the extent of genetic effects on brain fiber microstructure, based on tensor-derived measures, in 22 pairs of monozygotic (MZ) twins and 23 pairs of dizygotic (DZ) twins (90 scans). After Log-Euclidean denoising to remove rank-deficient tensors, DTI volumes were fluidly registered by high-dimensional mapping of co-registered MP-RAGE scans to a geometrically-centered mean neuroanatomical template. After tensor reorientation using the strain of the 3D fluid transformation, we computed two widely used scalar measures of fiber integrity: fractional anisotropy (FA), and geodesic anisotropy (GA), which measures the geodesic distance between tensors in the symmetric positive-definite tensor manifold. Spatial maps of intraclass correlations (r) between MZ and DZ twins were compared to compute maps of Falconer's heritability statistics, i.e. the proportion of population variance explainable by genetic differences among individuals. Cumulative distribution plots (CDF) of effect sizes showed that the manifold measure, GA, comparably the Euclidean measure, FA, in detecting genetic correlations. While maps were relatively noisy, the CDFs showed promise for detecting genetic influences on brain fiber integrity as the current sample expands.

TlCaBa2Cu2O7: The 1122 (90 K) superconductor in the new Tl(Ca,Ba)n+1CunO2n+3 seriesstar, open

The 1122 (n=2) member of the Tl(Ca,Ba)n+1CunO2n+3 series containing a single Tl-O layer is shown to be associated with a Tc of 90 K. This value of Tc is significantly lower than that of the 2122 phase (Tcnot, vert, similar110 K) with two Tl-O layers.

Three-dimensional structure of heat shock protein 90 from Plasmodium falciparum: molecular modelling approach to rational drug design against malaria

We have recently implicated heat shock protein 90 from Plasmodium falciparum (PfHsp90) as a potential drug target against malaria. Using inhibitors specific to the nucleotide binding domain of Hsp90, we have shown potent growth inhibitory effects on development of malarial parasite in human erythrocytes. To gain better understanding of the vital role played by PfHsp90 in parasite growth, we have modeled its three dimensional structure using recently described full length structure of yeast Hsp90. Sequence similarity found between PfHsp90 and yeast Hsp90 allowed us to model the core structure with high confidence. The superimposition of the predicted structure with that of the template yeast Hsp90 structure reveals an RMSD of 3.31 angstrom. The N-terminal and middle domains showed the least RMSD (1.76 angstrom) while the more divergent C-terminus showed a greater RMSD (2.84 angstrom) with respect to the template. The structure shows overall conservation of domains involved in nucleotide binding, ATPase activity, co-chaperone binding as well as inter-subunit interactions. Important co-chaperones known to modulate Hsp90 function in other eukaryotes are conserved in malarial parasite as well. An acidic stretch of amino acids found in the linker region, which is uniquely extended in PfHsp90 could not be modeled in this structure suggesting a flexible conformation. Our results provide a basis to compare the overall structure and functional pathways dependent on PfHsp90 in malarial parasite. Further analysis of differences found between human and parasite Hsp90 may make it possible to design inhibitors targeted specifically against malaria.

Heat Shock Protein 90 as a Drug Target against Protozoan Infections Biochemical characterization of HSP90 From plasmodium falciparum and trypanosoma evansi and evaluation of its inhibitor as a candidate drug

Using a pharmacological inhibitor of Hsp90 in cultured malarial parasite, we have previously implicated Plasmodium falciparum Hsp90 (PfHsp90) as a drug target against malaria. In this study, we have biochemically characterized PfHsp90 in terms of its ATPase activity and interaction with its inhibitor geldanamycin (GA) and evaluated its potential as a drug target in a preclinical mouse model of malaria. In addition, we have explored the potential of Hsp90 inhibitors as drugs for the treatment of Trypanosoma infection in animals. Our studies with full-length PfHsp90 showed it to have the highest ATPase activity of all known Hsp90s; its ATPase activity was 6 times higher than that of human Hsp90. Also, GA brought about more robust inhibition of PfHsp90 ATPase activity as compared with human Hsp90. Mass spectrometric analysis of PfHsp90 expressed in P. falciparum identified a site of acetylation that overlapped with Aha1 and p23 binding domain, suggesting its role in modulating Hsp90 multichaperone complex assembly. Indeed, treatment of P. falciparum cultures with a histone deacetylase inhibitor resulted in a partial dissociation of PfHsp90 complex. Furthermore, we found a well known, semisynthetic Hsp90 inhibitor, namely 17-(allylamino)-17-demethoxygeldanamycin, to be effective in attenuating parasite growth and prolonging survival in a mouse model of malaria. We also characterized GA binding to Hsp90 from another protozoan parasite, namely Trypanosoma evansi. We found 17-(allylamino)-17-demethoxygeldanamycin to potently inhibit T. evansi growth in a mouse model of trypanosomiasis. In all, our biochemical characterization, drug interaction, and animal studies supported Hsp90 as a drug target and its inhibitor as a potential drug against protozoan diseases.

Post-transcriptional Repair of a Split Heat Shock Protein 90 Gene by mRNA trans-Splicing

Heat shock protein 90 participates in diverse biological processes ranging from protein folding, cell cycle, signal transduction and development to evolution in all eukaryotes. It is also critically involved in regulating growth of protozoa such as Dictyostelium discoideum, Leishmania donovani, Plasmodium falciparum, Trypanosoma cruzi, and Trypanosoma evansi. Selective inhibition of Hsp90 has also been explored as an intervention strategy against important human diseases such as cancer, malaria, or trypanosomiasis. Giardia lamblia, a simple protozoan parasite of humans and animals, is an important cause of diarrheal disease with significant morbidity and some mortality in tropical countries. Here we show that the G. lamblia cytosolic hsp90 ( glhsp90) is split in two similar sized fragments located 777 kb apart on the same scaffold. Intrigued by this unique arrangement, which appears to be specific for the Giardiinae, we have investigated the biosynthesis of GlHsp90. We used genome sequencing to confirm the split nature of the giardial hsp90. However, a specific antibody raised against the peptide detected a product with a mass of about 80 kDa, suggesting a post-transcriptional rescue of the genomic defect. We show evidence for the joining of the two independent Hsp90 transcripts in-trans to one long mature mRNA presumably by RNA splicing. The splicing junction carries hallmarks of classical cis-spliced introns, suggesting that the regular cis-splicing machinery may be sufficient for repair of the open reading frame. A complementary 26-nt sequence in the ``intron'' regions adjacent to the splice sites may assist in positioning the two pre-mRNAs for processing. This is the first example of post-transcriptional rescue of a split gene by trans-splicing.

Turbulent heat flux variation over the Monsoon-Trough region during MONTBLEX-90

Tower data collected during the Monsoon-Trough Boundary Layer Experiment (MONTBLEX-90) have been analysed to understand the observed structure of the surface layer over an arid region (Jodhpur) and a moist region (Kharagpur) during active and weak phases of the 1990 southwest monsoon. Turbulent heat and momentum fluxes are estimated by the eddy correlation method using sonic data. The turbulent momentum flux at both Jodhpur and Kharagpur was larger when the winds were stronger, reaching a maximum of the order of 0.5 N m(-2) on 5 and 6 August when a low pressure system was located over the region. The heat flux at Jodhpur is high during weak monsoon days, the maximum being 450 W m(-2), whereas during active days the flux never exceeds 200 W m(-2). At Kharagpur, the flux does not vary significantly between active and weak monsoon days, the maximum in either phase being 160 W m(-2) At Jodhpur, there is significant contrast in the near-surface air temperature, being higher during weak monsoon days as compared to active days. Cloud cover did not vary significantly in both the regions. The turbulent heat flux variation at both the sites appears to be correlated mainly with soil mixture, and less sensitive to cloud cover.